P1288: UNMANIPULATED PERIPHERAL HAPLOIDENTICAL HAEMATOPOIETIC STEM CELL TRANSPLANT IS AN EFFECTIVE CONSOLIDATIVE STRATEGY FOR HIGH-RISK ACUTE MYELOID LEUKAEMIA AND MYELODYSPLASTIC SYNDROME
Authors: Fabio Serpenti, Daniele Avenoso, Kenyon Michelle, Pramila Krishnamurthy, Varun Mehra, Austin Kulasekararaj, Shreyans Gandhi, Francesco Dazzi, Shah Mili Naresh, Ye Ting Leung, Sandra Anteh, Madson Correia de Farias, Styliani Bouziana, Christianne Bourlon, Oana Diana Dragoi, Tony Pagliuca, Victoria Potter
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Consolidative strategy for high-risk acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) still relies on the curative effect of graft-versus-leukaemia(GVL) reaction following allogeneic stem cell transplant (allo-HSCT). Despite the improvement in the HLA tissue typing and mismatched unrelated donor transplants, a proportion of patients needing an allo-HSCT will still lack a donor and the debate on which alternative donor is most suitable is still active. Aims: Herein we report the outcome of patients affected with AML and MDS transplanted following haploidentical stem cell transplant (haplo-HSCT) at King’s College Hospital, London, between August 2010 and August 2021. Methods: Haplo-HSCT was performed using GCSF-mobilized peripheral blood stem cells(PBSC) as consolidative strategy for patients in complete morphological remission. Conditioning regimens were with cyclophosphamide 29mg/Kg, fludarabine 150mg/m2 and 200cGy Total Body Irradiation(FCTBI)or with thiotepa 10mg/Kg, fludarabine150 mg/m2, busulphan 9.6mg/kg (TBF). GVHD prophylaxis consisted of post-transplant cyclophosphamide(50 mg/kg day +3 and +4), mycophenolate and tacrolimus. Patients received FCTBI or TBF based on HCT-CI score and upper age limit of 65 for myeloablative conditioning. Probabilities of overall survival(OS) and GVHD-relapse-free survival (GRFS)was calculated using the Kaplan-Meier method.Relapse incidence(RI) and transplant-related mortality(TRM) rates were estimated using cumulative incidence(CI) functions and considered as competing risks.For GvHD, death and relapse were considered competing events. Statistical analyses were performed with GraphPad Prism Version9.4.1. Results: Forty patients with a median age of 50(range 21-69) and affected with high-risk myeloid malignancies were identified for this study (AML n=28, MDS n=12). Most patients(82%)received conditioning with FCTBI, and the remaining had TBF(18%). A median of 6.1x106 CD34+/Kg was infused(range3.37–14.26).Median time to neutrophil >1000/uL was 18days(13-42), and 25 days(14-44) to platelets>20.000/uL. Two cases of primary graft failure occurred. Median unfractionated, CD3+ and CD15 chimerism at 365days after transplant were 99%, 100% and 100% donor, respectively.One year and three years OS were62% and43%, respectively with a median OS of 22 months. One year and 3y GFRS were 47%and 34%, respectively. The global CI of relapse was 17%with a median time to relapse of 4 months(range 2-14). Incidence of acute GVHD was 22%(grade I/II);two cases of grade III were diagnosed. Chronic GVHD occurred in 17% of patients; moderate and severe cases were noted in 2 and 5 patients, respectively. TRM was37%, with a median time to TRM of 18 months(range 1-49). The main causes of death were infections(10 cases), GVHD(5 cases), disease progression(8 cases), and post-transplant lymphoproliferative disorder(1 case).CMV reactivation occurred in 50% of patients with a median time to first CMV reactivation of 46 days (range 13 – 415).No case of CMV disease occurred. Summary/Conclusion: This study shows that unmanipulated haplo-HSCT is a feasible and safe strategy for patients affected with high-risk AML and MDS.Despite the administration of reduced-intensity conditioning in most patients, the relatively low relapse rate is indirect proof of the curative effect of haplo-GVL. Our experience further confirms the safety of haplo-PBSC when the GVHD prophylaxis relies on post-transplant cyclophosphamide combined with mycophenolate and tacrolimus. Future efforts are needed to decrease the TRM mainly resulting from septic events due to the profound immune dysregulation and slow immune recovery following haplo-HSCT.Keywords: Haploidentical stem cell transplantation, Acute myeloid leukemia, Allogeneic bone marrow transplant